WO 2007/022531
`
`PCT/US2006/032719
`
`Xaais Glyi7 Cysig Xaajy Xaag9 Xaay (I) or Cys Cys Glu Xaay Cys Cys Asn Pro Ala Cys
`Thr Gly Cys Xaayq (SEQ ID NO:XXX)as desoribed herein.
`
`The peptide can be administered in combination with one or more agents for treatment of
`congestive heart failure, for example,a natriuretic peptide such asatrial natriuretic
`peptide, brain natriuretic peptide or C-type natriuretic peptide), a diuretic, or an inhibitor
`of angiotensin converting enzyme.
`
`In a fifteenth aspect, the invention features a methodfor treating benign prostatic
`hyperplasia, the method comprising administering to a patient a pharmaceutical
`composition comprising a purified peptide comprising, consisting of or consisting
`essentially ofthe amino acid sequence: Xaay Xaa, Kaa; Xaay Kaas Cys¢ Cys7 Xaag Kaa
`Cysio Cysii Xaaj, Xaay3 Xaaiy Cysis Xaayg Xaay7 Cysig Xaay9 Xaay9 Kaa. (1) or Xaay
`Kaa, Kaag Xaaq Kaas Cyse Cys; Xadg Xaag Cysio Cysi; Astys Prois Alayg Cysis Xaaig
`Gly,7 Cysig Xaayy Kaag9 Xaaq: (IL) or Cys Cys Glu Xaay Cys Cys Asn Pro Ala Cys Thr
`Gly Cys Xaay4 (SEQ ID NO:XXX)as described herein. The peptide can be administered
`alone or in combination with another agent for treatment ofBPH, for example, a 5-alpha
`reductase inhibitor(¢.g., finasteride) or an alpha adrenergic inhibitor (¢.g., doxazosine).
`
`In a sixteenth aspect,the invention features a methodfortreating or reducing pain,
`includingvisceral pain, pain associated with agastrointestinal disorder or pain associated
`with some other disorder, the method comprising administering to a patient a
`pharmaceutical composition comprising or consisting essentially of apurified peptide
`comprising, consisting of or consisting essentially of the amino acid sequence: Xaa; Xaaz
`Xaagz Xaaq Maas Cys¢ Cys7 Xaag Xaag Cysig Cysi1 AaaKaa; Kaay4 Cyss Kaaig Kaary
`Cysig Kaaiy Kaden Xaags (1) or Kaa, Kaa, Xaa3 Xaay Kaas Cys¢ Cys7 Xaag Kaay Cysio .
`Cys; Asmy2 Proy; Alayy Cysys Xaayg Gly; Cysyg Xaajo Kado Xaaq; (ID or Cys Cys Glu
`Xaay Cys Cys Asn Pro Ala Cys Thr Gly Cys Xaay4 (SEQ ID NO:XXX) as described
`herein.
`
`10
`
`45
`
`20
`
`25
`
`-30~
`
`MYLAN - EXHIBIT 1022 Part 2 of 16
`0450
`
`0450
`
`MYLAN - EXHIBIT 1022 Part 2 of 16
`
`

`

`WO 2007/022531
`
`a
`
`PCT/US2006/032719
`
`In a seventeenth aspect, the invention features a method for treating inflammation,
`including inflammation of the gastrointestinal tract, ¢.g., inflammation associated with a
`gastrointestinal disorderor infection or some otherdisorder, the method comprising
`administering to a patient a pharmaceutical composition comprising a purified peptide
`comprising, consisting of or consisting essentially ofthe amino acid sequence: Kaa; Xaay
`Xaa; Xaay Xaas Cys Cys7 Xaag Xaay Cysiq Cysy1 Xaay, Xaaj; Xaayy Cysys Xaayg Kaas
`Cysig Xaajy Xaayo Kaa, (I) or Kaa Xaay Xaaz Xaay Kaas Cyss Cys7 Kaag Xaay Cysio
`Cysi1 Asny2 Proy3 Alaa Cysis Xaaig Gly17 Cysig Xaai9 Xaago Xaag, (Il) or Cys Cys Glu
`Xaa4 Cys Cys Asn Pro Ala Cys Thr Gly Cys Xaa4 (SEQ ID NO:XXX)as described
`herein,
`
`In an eighteenth aspect, the invention features a methodfortreating congestive
`heart failure, the method comprising administering a complete or partial agonist of the
`intestinal guanylate cyclase (GC-C) receptor, Thus,the invention features a method for
`
`treating congestive heart failure, the method comprising administering to a patient a
`pharmaceutical composition comprising a purified peptide comprising, consisting of or
`consisting essentially of the amino acid sequence: Xaa; Xaa,Xaa; Xaag Xaas Cyse Cys7
`Xaag Xaag Cys1o Cysi1 Xaayz Xaajs Xaajq Cysys Xaayg Xaay7 Cysig Kaayg Kady Xaagy(I)
`or Xaa; Xaay Kaas Xaay Xaas Cys, Cys; Xaag Xaay Cysio Cys,; Asmy2 Proy3 Alays Cysy5
`. Xaaig Glyi7 Cysig Xaaiy Xaa29Xaag: (I) or Cys Cys Glu Xaay Cys Cys Asn Pro Ala Cys
`Thr Gly Cys Xaaj4 (SEQ ID NO:XXX)as described herein, The agonist/peptide can be
`administered alone or in combination with another agent for treatmentof congestive heart
`failure, for example, a natriuretic peptide suchas atrial natriuretic peptide, brain
`natriuretic peptide or C-typenatriuretic peptide, a diuretic, or an inhibitor of angiotensin
`converting enzymic. In various embodiments the congestive heart failure is categorized
`as Class II congestive heart failure; the congestive heart failure is categorized as Class I
`congestive heart failure; and the congestive heart failure is categorized as Class IV
`congestive heart failure. The New York Heart Association (NYHA) functional
`
`10
`
`15
`
`20
`
`26
`
`-~31-
`
`0451
`
`

`

`WO 2007/022531
`
`PCT/US2006/032719
`
`classification system relates congestive heart failure symptoms to everydayactivities and
`the patient's quality oflife. The NYHA defines the classes ofpatient symptomsrelating
`to congestive heart failure as: Class Il-slight limitation of physical activity, comfortable
`at rest, but ordinary physical activity results in fatigue, palpitation, or dyspnea; Class [I-
`marked limitation ofphysical activity, comfortable at rest, but less than ordinary activity
`causes fatigue, palpitation, or dyspnea and Class IV- unableto carry out any physical
`activity without discomfort, symptoms of cardiac insufficiencyat rest, ifany physical
`activity is undertaken, discomfort is increased. Heart failure treatment using the
`polypeptides and methods described herein can also be classified accordingto the
`ACC/AHA guidelines (Stage A: At risk for developing heart failure without evidence of
`cardiac dysfunction; Stage B: Evidence of cardiac dysfunction without symptoms; Stage
`C: Evidenceof cardiac dysfunction with symptoms! and Stage D: Symptoms ofheart
`failure despite maximal therapy).
`
`Tn a nineteenth aspect, the invention features a method for treating BPH, the method
`comprising administering a complete or partial agonist ofthe intestinal guanylate cyclase
`(GC-C) receptor, The agonist can be administered alone or in combination with another
`agent fortreatment ofBPH,for example, a 5-alpha reductase inhibitor(¢.g., finasteride)
`or an alpha adrenergic inhibitor (e.g., doxazosine),
`
`Ina twentieth aspect, the invention features isolated nucleic acid molecules comprising a
`sequence encoding’a peptide described herein, Also within the invention are vectors,
`e.g., expression vectors that include such nucleic acid molecules and can be used to
`express a peptide described herein in a cultured cell (¢.g., a eukaryotice cell or a
`prokaryotic cell), The vector can further include one or more regulatory elements, ¢.g., a
`heterologous promoter or elements required for translation operably linkedto the .
`sequence encoding the peptide. In some cases the nucleic acid molecule will encode an
`amino acid sequence that includes the amino acid sequenceof a peptide described herein.
`For example, the nucleic acid molecule can encodea preprotein or a preproprotein that
`
`10
`
`15
`
`20
`
`25
`
`-32
`
`0452
`
`0452
`
`

`

`WO 2007/022531
`
`.
`
`PCT/US2006/032719
`
`can be processed to produce a peptide described herein. In cases where unnatural amino
`acids are present in the polypeptides described herein, selector codons can be utilized in
`the synthesis of such polypeptides similar to that described in US20060019347 (for
`example, paragraphs 398-408, 457-499, and 576-588) herein incorporated by reference.
`
`A vectorthat includes a nucleotide sequence encoding a peptide described herein or a
`peptide or polypeptide comprising a peptide described herein may be either RNA or
`DNA,single- or double-stranded, prokaryotic, eukaryotic, or viral, Vectors can include
`transposons, viral vectors, episomes,(€.g., plasmids), chromosomesinserts, andartificial
`chromosomes(e.g. BACs or YACs), Suitable bacterial hosts for expression of the
`
`encode peptide or polypeptide include, but are not limited to, Z, coli. Suitable eukaryotic
`
`hosts include yeast such as S. cerevisiae, other fungi, vertebrate cells, invertebrate cells
`(e.g,, insect cells), plant cells, human cells, human tissue cells, and whole eukaryotic
`organisms, (¢.g,, a transgenic plant or a transgenic animal). Further, the vector nucleic
`_acid can be used to transfect a virus such as vaccinia or baculovirus (for example using
`
`the Bac-to-Bac® Baculovirus expression system (Invitrogen Life Technologies,
`
`Carlsbad, CA)).
`
`20
`
`As noted above the invention includes vectors and genetic constructs suitable for
`production of a peptide described herein or a peptide or polypeptide comprising such a
`peptide. Generally, the genetic construct algo includes, in addition to the encoding
`nucleic acid molecule, elements that allow expression, such as a promoter and regulatory
`
`: sequences. The expression vectorsmay contain transcriptional control sequences that
`control transcriptional initiation, such as promoter, enhancer, operator, and repressor
`
`25
`
`sequences. A variety of transcriptional contro! sequences are well known to those in the
`
`art and may be functional in, but are not limited to, a bacterium, yeast, plant, or animal
`cell, The expression vector can also include a translation tegulatory sequence(e.g., an
`untranslated. 5' sequence, an untranslated 3’ sequence, a poly A addition site, or an
`internal ribosomeentry site), a splicing sequenceor splicing regulatory sequence, and a
`
`~33 ~
`
`0453
`
`0453
`
`

`

`WO 2007/022531
`
`PCT/US2006/032719
`
`transcription termination sequence. The vector can be capable of autonomousreplication
`or it can integrate into host DNA.
`
`Lae
`
`The invention also includes isolated host cells harboring one of the forgoing nucleic acid
`molecules and methodsfor producing a peptide by culturing such a cell and recovering
`the peptide or a precursor ofthe peptide. Recovery of the peptide or precursor may refer
`to collecting the growth solution and need not involve additional steps ofpurification.
`Proteins of the present invention, however, can be purified using standard purification
`techniques, such as, but not limited to, affinity chromatography, thermaprecipitation,
`immunoaffinity chromatography, ammonium sulfate precipitation, ion exchange
`chromatography, filtration, electrophoresis and hydrophobic interaction chromatography.
`
`The peptides can be purified, Purified peptides are peptides separated from other
`proteins, lipids, and nucleic acidsor from the compoundsfrom whichis it synthesized.
`The polypeptide can constitute at least 10, 20, 50 70, 80 or 95% by dry weight ofthe
`purified preparation.
`
`In a twenty-first aspect, the invention features a method of increasing the level of cyclic
`guanosine 3’-monophosphate (cGMP) in an organ,tissue(¢.g, the intestinal mucosa), or
`
`cell (e.g., a cell bearing GC-A receptor) by administering to a patient a composition
`comprising or consisting essentially of apurified peptide comprising, consisting of or
`consisting essentially of the amino acid sequence: Xaa; Xaa2 Kaa3 Xaay Naas Cys— Cys7
`Xaag Kado Cysig Cysy) aay Xaai3 KaaCysisXaayo Kaa Cysig Xaais Xaagyaa()
`‘or Xaa; Xaa, Xaa3 KaayKaas Cysg Cys7 Xaag Xaag Cysio Cysi; Ast, Proy3 Alayy Cysis
`Kaays Glyi7 Cys}g Xaajy Xaagy Kaa(I) or Cys Cys Glu Xaaq Cys Cys Asn Pro Ala Cys
`Thr Gly Cys Xaay4 (SEQ ID NO:XXX)as described herein.
`
`In a twenty-second aspect, the invention features polypeptides comprising, consisting or
`consisting essentially ofthe amino acid sequence Xaa,Xaa, Kaa; Xaag Xaas Cysg Cysy
`
`10
`
`15
`
`20
`
`25
`
`-34.
`
`0454
`
`0454
`
`

`

`WO 2007/022531
`
`PCT/US2006032719
`
`Xaag Xaay Cysio Cysi; Xaaie Xaary Xaay4 Cysys Xaajs Kaay7 Cysig Xaaig Kaan Kaan)
`where: a) Xaag or Kady is not present; b) neither Xaag or Xaao is present; c) one of
`Xaar, Xaais and Xaayais not present; d) two ofXaay2, Xaars and Xaayq are not present; e)
`three of Xaajz, Xaaj3 and Xaay4 are not present; f) one of Xaays and Xaaj7 is not present;
`
`g) neither Xaay¢ or Xaaj7 is present and combinations thereof. In various embodiments,
`one, two, three, four or five of Xaa; Xaag Xaa3 Kaa, and Xaas are not present, In other
`
`embodiments, one, two or three or Xaaj9 Xaay9 and Xaag; are missing,
`
`10
`
`16
`
`In twenty third aspect, the invention features a method for treating a disorder ameliorated
`by increasing cGMP levels, the method comprising administering a pharmaceutical
`composition comprising, consisting essentially of or consisting of a peptide or agonist
`described herein and a pharmaceutically acceptable carrier.
`
`In a twenty-fourth aspect, the invention features a method for treating hypertension. The.
`method comprises: administering to the patient a pharmaceutical composition
`. comprising, consisting essentially of, or consisting of a peptide or agonist described
`herein and a pharmaceutically acceptable carrier. The composition can be administered
`in combination with another agentfor treatment of hypertension, for example,a diuretic,
`an ACEinhibitor, an angiotensin receptor blocker, a beta-blocker, or a calcium channel
`
`20
`
`blocker.
`
`25
`
`In a twenty-fifth aspect, the invention features a method for treating secondary:
`hyperglycemias in connection with pancreatic diseases (chronic pancreatitis,
`pancreasectomy, hemochromatosis) or endocrine diseases (acromegaly, Cushing's
`syndrome, pheochromocytomaor yperthyreosis), drug-induced hyperglycemias
`_(benzothiadiazine saluretics, diazoxide or glucocorticoids), pathologic glucose tolerance,
`hyperglycemias, dyslipoproteinemias, adiposity, hyperlipoproteinemias and/or
`hypotensions is described. The method comprises: administering to the patient a
`
`-35~
`
`
`
`0455
`
`0455
`
`

`

`
`
`WO 2007/022531
`
`PCT/US2006/032719
`
`pharmaceutical composition comprising, consisting essentially of, or consisting of a
`peptide or agonist described herein and a pharmaceutically acceptable carrier.
`
`In a twenty-sixth aspect, the invention features a method for decreasing
`gastrointestinal pain or visceral pain in a patient, the method comprising: administering to
`the patient a pharmaceutical composition comprising, consisting essentially of, or
`consisting of SEQ ID NO,3 (or another peptide described herein) and a pharmaceutically
`acceptable carrier
`
`10
`
`15
`
`20
`
`25
`
`Amongthe useful peptides are peptides comprising, consisting of or consisting
`essentially of the amino acid sequence Xaa; Xaa2 Xaa3 Xaaq Xaas Cys Cys Glu Xaay Cys
`Cys Asn Pro AlaCys Thr Gly Cys Tyr Xaagq Xaay: (I) (SEQ 1D NO:---) are the
`- following peptides:
`Gin Ser Ser Asn Tyr Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (SEQ ID NO:---)
`Asn Thr Ser Asn Tyr Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (SEQ ID NO}--~
`
`°
`)
`Asn Leu Ser Asn Tyr Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (SEQ ID NO:---
`
`,
`)
`Asn lle Ser Asn Tyr Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (SEQ ID NO:---)
`Asn Ser Ser Gln Tyr Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (SEQ ID NO;---)
`Ser Ser Asn Tyr Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (SEQ ID NO:---)
`Gin Ser Ser Gln Tyr Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (SEQ ID NO:---)
`Ser Ser Gin Tyr Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Tht Gly Cys Tyr (SEQ ID NO:---),
`Asn Ser Ser Asn Tyr Cys Cys Glu Ala Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (SEQ ID NO:
`
`).
`Asn Ser Ser Asn Tyr Cys Cys Glu Arg Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (SEQ ID NO; )
`Asn Ser SerAsn Tyr Cys Cys Glu Asn Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (SEQ IDNO: )
`Asn Ser Ser Asn Tyr Cys Cys Glu Asp Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (SEQ ID NO: )
`Asn Ser Ser Asn Tyr Cys Cys Gin Cys Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (SEQ ID NO: )
`
`~ 36+
`
`0456
`
`0456
`
`

`

`WO 2007/022531
`
`PCT/U82006/032719
`
`Asn Ser Ser Asn Tyr Cys Cys Glu Gin Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (SEQ ID NO: )
`AsnSer SerAsn Tyr Cys Cys Glu Glu Cys Cys Asn ProAla Cys Thr Gly Cys Tyr (SEQ ID NO: )
`Asn Ser Ser Asn Tyr Cys Cys Glu Gly Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (SEQ ID NO: )
`Asn Ser SerAsn Tyr Cys Cys Glu His Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (SEQ ID NO: )
`Asn Ser SerAsn Tyr Cys Cys Glu Ile Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (SEQ ID NO:
`)
`Asn Ser SerAsn Tyr Cys Cys Glu Lys Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (SEQ ID NO: )
`Asn Ser SerAsn Tyr Cys Cys Glu Met Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (SEQ ID NO: )
`Asn Ser Ser Asn Tyr Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (SEQ ID NO: )
`Asn Ser Ser Asn Tyr Cys Cys Glu Pro Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (SEQ ID NO: )
`Asn Ser Ser Asn Tyr Cys Cys Glu Ser Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (SEQ ID NO: )
`Asn Ser Ser Asn Tyr Cys Cys Glu Thr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (SEQ ID NO: )
`Asn Ser Ser Asn Tyr Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (SEQ ID NO: )
`Asn Ser Ser Asn Tyr Cys Cys Glu Val Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (SEQ ID NO;
`)
`Cys Cys Glu Ala Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (SEQ ID NO: )
`Cys Cys Glu Arg Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (SEQ ID NO: )
`Cys Cys Glu Asn Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (SEQ ID NO:
`Cys Cys Glu Asp Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (SEQ ID NO:
`Cys Cys Gln Cys Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (SEQ ID NO:
`" Cys Cys Glu Gln Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (SEQ ID NO:
`Cys Cys Glu Glu Cys Cys Asn Pro AlaCys Thr Gly Cys Tyr (SEQ ID NO:
`Cys Cys Glu Gly Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (SEQ ID NO:
`Cys Cys Glu His Cys Cys Asn Pro Ala Cys Thr GlyCys Tyr (SEQ ID NO:
`Cys Cys Glu Ile Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (SEQ ID NO:
`)
`Cys Cys Glu Lys Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (SEQ ID NO;
`Cys Cys Glu Met Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (SEQ ID NO: )
`Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (SEQ ID NO:)-
`Cys Cys Glu Pro Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (SEQ ID NO: )
`Cys Cys Glu Ser Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (SEQ ID NO: )
`Cys Cys Glu Thr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (SEQ ID NO: }
`4
`
`emeeae”
`
`)
`
`10
`
`15
`
`20
`
`26
`
`~37-
`
`0457
`
`0457
`
`

`

`WO 2007/022531
`
`PCT/US2006/032719
`
`Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (SEQ ID NO: )
`Cys Cys Glu Val Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr (SEQ ID NO: )
`Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys ‘Thr Gly Cys (SEQ ID NO:6 )
`Cys Cys Glu Ala Cys Cys Asn Pro Ala Cys Thr Gly Cys (SEQ ID NO: )
`Cys Cys Glu Arg Cys Cys Asn Pro Ala Cys Thr Gly Cys (SEQ ID NO:)
`Cys Cys Glu Asn Cys Cys Asn Pro Ala Cys Thr Gly Cys (SEQ ID NO: )
`Cys Cys Glu Asp Cys Cys Asn Pro Ala Cys Thr Gly Cys (SEQ ID NO; )
`Cys Cys Glu Cys Cys Cys Asn Pro Ala Cys Thr Gly Cys (SEQ ID NO: )
`Cys Cys Glu Gin Cys Cys Asn Pro Ala Cys Thr Gly Cys (SEQ ID NO:)
`~ Cys Cys Glu Glu Cys Cys Asn Pro Ala Cys Thr Gly Cys (SEQ ID NO: )
`Cys Cys Glu Gly Cys Cys Asn Pro Ala Cys Thr Gly Cys (SEQ ID NO;
`)
`Cys Cys Glu His Cys Cys Asn Pro Ala Cys Thr Gly Cys (SEQ ID NO: )
`Cys Cys Glu Ile Cys Cys Asn Pro Ala Cys Thr Gly Cys (SEQID NO:)
`Cys Cys Glu Lys Cys Cys Asn Pro Ala Cys Thr Gly Cys (SEQ ID NO: )
`Cys Cys Giu Met Cys Cys Asn Pro Ala Cys Thr Gly Cys (SEQ ID NO:)
`Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys (SEQ ID NO: )
`Cys Cys Glu Pro Cys Cys Asn Pro Ala Cys Thr Gly Cys (SEQ ID NO: )
`Cys Cys Glu Ser Cys Cys Asn Pro Ala Cys Thr Gly Cys (SEQ ID NO;
`)
`Cys Cys Glu Thr Cys Cys Asn Pro Ala Cys Thr Gly Cys; (SEQ ID NO; }
`Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Thr Gly Cys (SEQ ID NO:)
`_ Cys Cys Glu Val Cys Cys Asn Pro Ala Cys Thr Gly Cys (SEQ ID NO:)..
`
`Also useful are peptides comprising, consisting of or consisting essentially of any ofthe
`following sequences:
`
`Cys Cys Glu Leu Cys Cys Ala Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Glu Leu Cys Cys Val Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Glu Leu Cys Cys Leu Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Glu Leu Cys CysHe Pro Ala Cys Thr Gly. Cys Tyr
`Cys Cys Giu Leu Cys Cys Pro Pro Ala Cys Thr Gly Cys Tyr
`
`- 38 -
`
`40
`
`8
`
`20
`
`25
`
`0458
`
`0458
`
`

`

`WO 2007/022531
`
`PCT/U82006/032719
`
`Cys Cys Glu Leu Cys Cys Met Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Glu Leu Cys Cys Phe Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Giu Leu Cys Cys Trp Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Glu Leu Cys Cys Gly Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Glu Leu Cys Cys Ser Pro Ala Cys Thr Gly:Cys Tyr
`Cys Cys Glu Leu Cys Cys Thr Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Glu Leu Cys Cys Cys Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Glu Leu Cys Cys Gin Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Glu Leu Cys Cys Tyr Pro Ala Cys Thr Gly Cys Tyr
`| Cys Cys Glu Leu Cys Cys Asp Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Glu Leu Cys Cys Glu Pro Ala Cys Thr Gly Cys Tyr
`~ Cys Cys Glu Leu Cys Cys Lys Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Glu Len Cys Cys Arg Pro Ala Cys Thr GlyCys Tyr
`Cys Cys Glu Leu Cys Cys His Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Glu Tyr Cys Cys Ala Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Glu Tyr Cys Cys Val Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Glu Tyr Cys Cys Leu Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Glu Tyr Cys Cys Ile Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Glu Tyr Cys Cys Pro Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Glu Tyr Cys Cys MetPro Ala Cys Thr Gly Cys Tyr
`Cys Cys Glu Tyr Cys Cys Phe Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Glu Tyr Cys Cys Trp Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Glu Tyr Cys Cys Gly Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Glu Tyr Cys Cys Ser Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Glu Tyr Cys Cys ThrPro Ala Cys Thr Gly Cys Tyr
`Cys Cys Glu Tyr Cys Cys Cys Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Glu Tyr Cys Cys Gln Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Glu Tyr Cys Cys Tyr Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Glu Tyr Cys Cys Asp Pro Ala Cys Thr Gly Cys Tyr
`
`40
`
`15
`
`20
`
`25
`
`-39-
`
`0459
`
`0459
`
`

`

`WO 2007/022531
`
`PCT/US2006/032719
`
`Cys Cys Glu Tyr Cys Cys Glu Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Glu Tyr Cys Cys Lys Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Glu Tyr Cys Cys Arg Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Glu Tyr Cys Cys His Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Glu Leu Cys Cys Ala Pro Ala Cys Thr Gly Cys
`' Cys Cys Glu Leu Cys Cys Val Pro Ala Cys Thr Gly Cys
`Cys Cys Glu Len Cys Cys Leu Pro Ala Cys Thr Gly Cys
`Cys Cys Glu Leu Cys Cys Ie Pro Ala Cys Thr Gly Cys
`Cys Cys Glu Leu Cys Cys Pro Pro Ala Cys Thr Gly Cys
`Cys Cys Glu Leu Cys Cys Met Pro Ala Cys Thr Gly Cys
`Cys Cys Glu Len Cys Cys Phe Pro Ala Cys Thr Gly Cys
`Cys Cys Glu Leu Cys Cys Trp Pro Ala Cys Thr Gly Cys
`Cys Cys Glu Len Cys Cys Gly Pro Ala Cys Thr Gly Cys
`. Cys Cys Glu Leu Cys Cys Ser Pro Ala Cys Thr Gly Cys
`Cys Cys Glu Leu Cys Cys Thr Pro Ala Cys Thr Gly Cys
`Cys Cys Glu Leu Cys Cys Cys Pro Ala Cys ThrGly Cys
`Cys Cys Glu Leu Cys Cys Gln Pro Ala Cys Thr Gly Cys
`Cys Cys Glu Len Cys Cys Tyr Pro Ala Cys Thr Gly Cys
`Cys Cys Gly Leu CysCys Asp Pro Ala Cys Thr Gly Cys
`Cys Cys Glu Len Cys Cys Glu Pro Ala Cys Thr Gly Cys
`Cys Cys Glu Leu Cys Cys Lys Pro Ala Cys Thr Gly Cys
`Cys Cys Glu Leu Cys Cys Arg Pro Ala Cys Thr Gly Cys
`Cys Cys Glu Leu Cys Cys His Pro Ala Cys Thr Gly Cys
`Cys Cys Glu Tyr Cys Cys Ala Pro Ala Cys Thr Gly Cys
`Cys Cys Glu Tyr Cys Cys Val Pro Ala Cys Thr Gly Cys
`Cys CysGlu Tyr Cys Cys Leu Pro Ala Cys Thr Gly Cys
`Cys Cys Glu Tyr Cys Cys Tle Pro Ala Cys Thr Gly Cys
`Cys Cys Glu Tyr Cys Cys Pro Pro Ala Cys Thr Gly Cys
`Cys Cys Glu Tyr Cys Cys Met Pro Ala Cys Thr Gly Cys
`
`49
`
`16
`
`20
`
`25
`
`~ 40 -
`
`0460
`
`0460
`
`

`

`WO 2007/022531
`
`PCT/0S82006/032719
`
`Cys Cys Glu Tyr Cys Cys Phe Pro Ala Cys Thr Gly Cys
`Cys Cys Glu Tyr Cys Cys Trp Pro Ala Cys Thr Gly Cys
`Cys Cys Glu Tyr Cys Cys Gly Pro Ala Cys Thr Gly Cys
`Cys Cys Glu Tyr Cys Cys Ser Pro Ala Cys Thr Gly Cys
`Cys Cys Glu Tyr Cys Cys Thy Pro Ala Cys Thr Gly Cys
`Cys Cys Glu Tyr Cys Cys Cys Pro Ala Cys Thr Gly Cys
`Cys Cys Glu Tyr Cys Cys Gin Pro Ala Cys Thr Gly Cys
`Cys Cys Glu Tyr Cys Cys Tyr'Pro Ala Cys Thr Gly Cys
`Cys Cys Glu Tyr Cys Cys Asp Pro Ala Cys ThrGly Cys
`Cys Cys Glu Tyr Cys Cys Glu Pro Ala Cys Thr Gly Cys
`Cys Cys Glu Tyr Cys Cys Lys Pro Ala Cys Thr Gly Cys
`"Cys Cys Glu Tyr Cys Cys Arg Pro Ala Cys Thr Gly Cys
`Cys Cys Glu Tyr Cys Cys His Pro Ala Cys Thr Gly Cys
`Cys Cys Glu Leu Cys Cys Asn Pro Thr Cys Thr Gly Cys Tyr
`Cys Cys Glu Tyr Cys Cys Asn Pro Thr Cys Thr Gly Cys Tyr
`_ Cys Cys Glu Leu Cys Cys Asn Pro Thr Cys Thr Gly Cys
`Cys Cys Glu Tyr Cys Cys Asn Pro Thr Cys Thr Gly Cys
`Cys Cys Glu Phe Cys Cys Asn Pro Thr Cys Thr Gly Cys Tyr
`Cys Cys Glu Phe Cys Cys Asn Pro Thr Cys Thr Gly Cys
`Cys Cys Glu Trp Cys Cys Asn Pro Thr Cys Thr Gly Cys Tyr
`Cys Cys Glu Trp Cys Cys Asn Pro Thr Cys Thr Gly Cys
`Cys Cys Glu Leu Cys Cys Asn Gly Ala Cys Thr Gly Cys Tyr
`Cys Cys Glu Tyr Cys Cys Asn Gly Ala Cys Thr Gly Cys Tyr
`Cys Cys Glu Leu Cys Cys Asn Gly Ala Cys Thr Gly Cys:
`Cys Cys Glu Tyr Cys Cys Asn Gly Ala Cys Thr Gly Cys
`- Cys Cys Glu Phe Cys Cys Asn Gly Ala Cys Thr Gly Cys Tyr
`Cys Cys Glu Phe Cys Cys Asn Gly Ala Cys Thr Gly Cys
`Cys Cys Glu Trp Cys Cys Asn Gly Ala Cys Thr Gly Cys Tyr
`Cys Cys Glu Trp Cys Cys Asn Gly Ala Cys Thr Gly Cys
`
`10
`
`15
`
`20
`
`25
`
`-4] -
`
`0461
`
`0461
`
`

`

`WO 2007/022531 -
`
`PCT/US2006/032719
`
`Cys Cys Glu Lev Cys Cys Asn Pro Ala Cys Val Gly Cys Tyr
`Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Val Gly Cys Tyr
`Cys Cys Gla Leu Cys Cys Asn Pro Ala Cys Val Gly Cys)
`Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Val Gly Cys
`Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Val Gly Cys Tyr
`Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Val Gly Cys
`Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Val Gly Cys Tyr
`Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Val Gly Cys
`Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Gly Gly Cys Tyr
`Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Gly Gly Cys Tyr
`Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Gly Gly Cys
`Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Gly Gly Cys
`Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Gly Gly Cys Tyr
`Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Gly Gly Cys
`Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Gly Gly Cys Tyr
`Cys Cys GluTrp Cys Cys Asn Pro Ala Cys Gly Gly Cys
`Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Ala Cys Tyr
`Cys Cys Glu Tyr Cys CysAsn Pro Ala Cys Thr Ala Cys Tyr
`Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Ala Cys
`Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Ala Cys
`Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Thr Ala Cys Tyr °
`Cys Cys Glu Trp Cys Cys Asn Pro Ala Cys Thr Ala Cys
`Cys Cys Glu PheCys Cys Asn Pro Ala Cys Thr Ala Cys Tyr
`Cys Cys Glu Phe Cys Cys Asn Pro Ala Cys Thr Ala Cys
`Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Ala
`Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Val
`Cys Cys Glu Len Cys Cys Asn Pro Ala Cys Thr Gly Cys Leu
`Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly CysIle
`Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Pro
`
`-42-
`
`10
`
`20
`
`25
`
`
`
`0462
`
`0462
`
`

`

`WO 2007/022531
`
`PCT/US2006/032719
`
`Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Met
`Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Phe
`Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Trp
`Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Gly
`
`Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Ser
`Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Thr
`Cys Cys Glu LeuCys Cys Asn Pro Ala Cys Thr Gly Cys Cys
`Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Asn
`
`Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Gln
`
`10
`
`Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Asp
`
`15
`
`20
`
`25°
`
`Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Glu
`
`Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Lys
`Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Arg
`Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys His
`Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Ala
`
`~
`
`Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Val
`Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Leu
`Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly CysIle
`Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Tbr Gly Cys Pro
`Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Met
`
`Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Phe
`Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Trp
`Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Gly
`
`Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Ser
`Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Thr
`Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Cys
`Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr GlyCys Asn
`Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Gln
`Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Asp
`
`~ 43 -
`
`0463
`
`0463
`
`

`

`WO 2007/022531
`
`PCT/US2006/032719
`
`Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Glu
`Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Lys
`Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Arg
`Cys Cys Glu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys His
`Cys Cys Ala Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Val Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Leu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr
`Cys Cyslle Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Met Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Phe Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Trp Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Gly Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Ser Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr
`Cys CysThr Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Cys Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Asn Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Gln Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr
`.Cys Cys Tyr Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Asp Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Lys Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Arg Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys His Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr
`_ Cys Cys Ala Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys
`Cys Cys Val Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys
`Cys Cys Leu Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys
`Cys CysTle Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys
`Cys Cys Met Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys
`Cys Cys Phe Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys
`Cys Cys Trp Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys
`
`-
`
`~ 44 -
`
`18
`
`20
`
`a)
`
`
`
`0464
`
`0464
`
`

`

`WO 2007/022531
`
`PCT/US2006/032719
`
`Cys Cys Gly Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys
`Cys Cys Ser Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys
`Cys Cys Thr Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys
`Cys Cys Cys Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys
`Cys Cys Asn Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys
`Cys Cys Gln Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys
`Cys Cys Tyr Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys
`Cys Cys Asp Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys
`Cys Cys Lys Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys
`Cys Cys Arg Leu Cys Cys Asn Pro Ala Cys Thr Gly'Cys
`Cys Cys His Leu Cys Cys Asn Pro Ala Cys Thr Gly Cys
`Cys Cys Ala Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Val Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr
`‘Cys Cys Leu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Tle Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Met Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Phe Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Trp Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Gly Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Ser Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Thr Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Cys Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Asn Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Gln Tyr Cys Cys Asn ProAla Cys Thr Gly Cys Tyr
`Cys Cys Tyr Tyr Cys Cys Asn Pro Ala CysThr Gly Cys Tyr
`Cys Cys Asp Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Lys Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Arg Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys His Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr
`
`- 45 -
`
`10
`
`18
`
`20
`
`25
`
`0465
`
`0465
`
`

`

`WO 2007/022531
`
`PCT/0S2006/032719
`
`Cys Cys Ala Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys
`Cys Cys Val Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys
`Cys Cys Leu Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys .
`Cys Cys lle Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys
`
`Cys Cys Met Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys
`Cys Cys Phe Tyr Cys Cys Asn Pro Ala Cys Tbr Gly Cys
`Cys Cys Trp Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys
`Cys Cys Gly Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys
`Cys Cys Ser Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys
`Cys Cys Thr Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys
`Cys Cys Cys Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys
`Cys Cys Asn Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys
`‘Cys Cys Gin Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys
`Cys Cys Tyr Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys
`Cys Cys Asp Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys
`Cys Cys Lys Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys
`Cys Cys Arg Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys
`
`Cys Cys His Tyr Cys Cys Asn Pro Ala Cys Thr Gly Cys
`
`Cys Cys Glu Phe Cys Cys Ala Pro Ala Cys Thr Gly Cys Tyr
`
`Cys Cys Glu Phe Cys Cys Val Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Glu Phe Cys Cys Leu Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Gin Phe Cys CysIle Pro Ala Cys Thr Gly Cys Tyr
`
`Cys Cys Glu Phe Cys Cys Pro Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Glu Phe Cys Cys Met Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Glu Phe Cys Cys Phe Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Glu Phe Cys Cys Trp Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Glu Phe Cys Cys Gly Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Glu Phe Cys Cys Ser Pro Ala Cys Thr Gly Cys Tyr
`Cys Cys Glu Phe Cys Cys Thr Pro Ala Cys Thr Gly Cys Tyr
`
`~4